Project Summary - Heme and hemoglobin utilization by Mycobacterium tuberculosis Mycobacterium tuberculosis (Mtb) is of one of the most important bacterial pathogens. Iron is essential for growth of Mtb, but iron is efficiently sequestered in the human host. Hemoglobin is by far the most prevalent iron source in the human body and is often preferred by bacterial pathogens. Recently, we identified proteins that are essential components of an unprecedented heme and hemoglobin utilization system in Mtb. Interestingly, these novel heme-binding proteins are also required for utilization of hemoglobin indicating that heme is released from hemoglobin at the cell surface of Mtb by an unknown mechanism and then transferred to the heme uptake system. This proposal aims to elucidate the molecular mechanisms of heme and hemoglobin utilization by Mtb. This project will lead to a better understanding of how Mtb gains access to iron during infection. To achieve these goals we employ state-of-the-art genetic, biochemical, biophysical and structural methods.